Stabilization of influenza virus vaccine

Abstract

This invention concerns stabilized influenza virus vaccines and a method of stabilizing influenza viruses and vaccines by the addition of protein hydrolysates and/or amino acids.

What is claimed is: 
     
       1. In a method for stabilizing the immunogenicity of neuraminidase and neuraminidase containing antiviral influenza vaccines neuromidase-stabilizing formulating the vaccine with an effective amount within the range of about 0.0% to about 4.0% w/v of an agent selected from the group consisting of protein hydrolysates, amino acids and combinations thereof. 
     
     
       2. The method of claim 1 wherein the protein hydrolysates are enzymatic digests of casein. 
     
     
       3. The method of claim 2 wherein the protein hydrolysate is N-Z AMINE® NAK or N-Z AMINE® A. 
     
     
       4. The method of claim 3 wherein the N-Z AMINE® NAK is present at a concentration of 0.2-4.0% by weight of the vaccine. 
     
     
       5. The method of claim 1 wherein the amino acids are selected from the group consisting of alanine, aspartic acid, glycine, histidine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, trytophan, valine, or mixtures thereof. 
     
     
       6. The method of claim 5 wherein the amino acids are histidine or proline, or mixtures thereof. 
     
     
       7. The method of claim 5 wherein the amino acids are present in a concentration of 0.01-4.0% by weight of the vaccine. 
     
     
       8. The method of claim 6 wherein the amino acids are present in a concentration of 0.01-4.0% by weight of the vaccine. 
     
     
       9. The method of claim 1 wherein the vaccine is a bispecific influenza vaccine selected from the group consisting of H1N1, H2N2, and N3N2. 
     
     
       10. The method of claim 1 wherein the vaccine is a monospecific influenza vaccine such as H7N1 or H7N2. 
     
     
       11. The method of claim 1 wherein the vaccine consists esssentially of purified neuraminidase of type N1 or type N2. 
     
     
       12. An improved influenza vaccine effective in eliciting the production of immunizing antibodies in mammals which vaccine contains viral neuraminidase, wherein the improvement consists essentially of a neuromidase stabilizer in said vaccine of a protein hydrolysate or at least one amino acid in sufficient neuromidase-stabilizing quantity within the range of about 0.0% to about 4.0% w/v to stabilize the enzymatic activity of the neuraminidase. 
     
     
       13. The improved vaccine as recited in claim 12 wherein the protein hydrolysate is a pancreatic digest of casein. 
     
     
       14. The improved vaccine as recited in claim 12 wherein the protein hydrolysate is N-Z AMINE NAK® or N-Z AMINE A®. 
     
     
       15. The improved vaccine as recited in claim 14 wherein N-Z AMINE NAK® or N-Z AMINE A® comprises about 0.01% to about 4.0% (w./v.). 
     
     
       16. The improved vaccine as recited in claim 12 wherein the amino acid is selected from the group consisting of alanine, aspartic acid, glycine, histidine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, trytophan, valine and mixtures thereof. 
     
     
       17. The improved vaccine as recited in claim 16 wherein the amino acid is histidine, proline or a mixture thereof. 
     
     
       18. The improved vaccine as recited in claim 16 wherein the amino acid comprises about 0.01% to about 4.0% (w./v.). 
     
     
       19. The improved vaccine as recited in claim 12 wherein the vaccine is a bispecific influenza vaccine selected from the group consisting of H1 N1, H2 N2 and H3N2 types. 
     
     
       20. The improved vaccine as recited in claim 12 wherein the vaccine is a monospecific influenza vaccine H7N1 or H7N2. 
     
     
       21. The improved vaccine as recited in claim 12 wherein the vaccine consists essentially of purified neuraminidase of type N1 or type N2.